Neuronal Signaling is involved in the regulation of the mechanics of the central nervous system such as its structure, function, genetics and physiology as well as how this can be applied to understand diseases of the nervous system. Every information processing system in the CNS is composed of neurons and glia, neurons have evolved unique capabilities for intracellular signaling (communication within the cell) and intercellular signaling (communication between cells).

G protein-coupled receptors (GPCRs), including 5-HT receptor, histamine receptor, opioid receptor, and etc, are the largest class of sensory proteins and are important therapeutic targets in Neuronal Signaling. GPCRs are activated by diverse stimuli, including light, enzymatic processing of their N-termini, and binding of proteins, peptides, or small molecules such as neurotransmitters, and regulate neuronal excitability by indirectly modulating the function of voltage-gated channels, such as voltage-gated calcium channel and transient receptor potential (TRP) ion channels. Besides, Notch signaling, such as β- and γ-secretase, also plays multiple roles in the development of the CNS including regulating neural stem cell (NSC) proliferation, survival, self-renewal and differentiation.

GPCR dysfunction caused by receptor mutations and environmental challenges contributes to many neurological diseases. Notch signaling in neurons, glia, and NSCs is also involved in pathological changes that occur in disorders such as stroke, Alzheimer's disease and CNS tumors. Thus, targeting Neuronal Signaling, such as notch signaling and GPCRs, can be used as therapeutic interventions for several different CNS disorders.

References:
[1] Lathia JD, et al. J Neurochem. 2008 Dec;107(6):1471-81.
[2] Palczewski K, et al. Annu Rev Neurosci. 2013 Jul 8;36:139-64.
[3] Geppetti P, et al. Neuron. 2015 Nov 18;88(4):635-49.


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H-9 dihydrochloride

H-9 Dihydrochloride is a PKA (protein kinase) inhibitor. H-9 Dihydrochloride (10 μM) significantly reduces the excitatory response to 5-HT. H-9 Dihydrochloride also has a direct effect on pharyngeal activity. H-9 Dihydrochloride inhibits signal-transduction and cell growth in EGF (epidermal growth factor)-dependent epithelial cell lines[1][2][3].

  • CAS Number: 116700-36-8
  • MF: C11H15Cl2N3O2S
  • MW: 324.227
  • Catalog: 5-HT Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: 250-255ºC dec.
  • Flash Point: N/A

L-663581

L-663581 (FG-8205) is an agonist of benzodiazepine receptor, acting as a partial agonist at GABA A receptor[1].

  • CAS Number: 122384-14-9
  • MF: C17H16ClN5O2
  • MW: 357.79400
  • Catalog: GABA Receptor
  • Density: 1.5g/cm3
  • Boiling Point: 624.1ºC at 760mmHg
  • Melting Point: N/A
  • Flash Point: 331.3ºC

Muscarine iodide

Muscarine ((+)-Muscarine) iodide is a toxin that can stimulate the parasympathetic nervous system. Muscarine iodide is a prototype muscarinic acetylcholine receptor agonist[1][2].

  • CAS Number: 24570-49-8
  • MF: C9H20INO2
  • MW: 301.16500
  • Catalog: mAChR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Kelatorphan

Kelatorphan is a full inhibitor of enkephalin degrading enzymes.

  • CAS Number: 92175-57-0
  • MF: C14H18N2O5
  • MW: 294.30300
  • Catalog: Opioid Receptor
  • Density: 1.301g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

TQS

TQS is a α7 nicotinic acetylcholine receptor (nAChR) positive allosteric modulator. TQS can be used for the research of neuroinflammatory pain[1].

  • CAS Number: 353483-92-8
  • MF: C22H20N2O2S
  • MW: 376.47100
  • Catalog: nAChR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

PYR-PHE-PHE-GLY-LEU-MET-NH2

[Glp6] Substance P (6-11) is an analogue of substance P (6-11). Substance P (6-11) stimulates [3H]-inositol monophosphate ([3H]-IP1) formation in rat urinary bladder by acting on the 'septide-sensitive' tachykinin receptors[1][2].

  • CAS Number: 61123-13-5
  • MF: C36H49N7O7S
  • MW: 723.88200
  • Catalog: Neurokinin Receptor
  • Density: 1.247g/cm3
  • Boiling Point: 1195.9ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 677ºC

Zamifenacin

Zamifenacin (UK-76654) is a potent gut-selective muscarinic M3 receptor antagonist. Zamifenacin significantly reduces colonic motility in irritable bowel syndrome[1].

  • CAS Number: 127308-82-1
  • MF: C27H29NO3
  • MW: 415.52400
  • Catalog: mAChR
  • Density: 1.2g/cm3
  • Boiling Point: 532.5ºC at 760mmHg
  • Melting Point: N/A
  • Flash Point: 145.6ºC

ELN 318463 racemate

ELN 318463 racemate is the racemate of ELN 318463. ELN 318463 is a selective gamma-secretase inhibitor.

  • CAS Number: 851599-82-1
  • MF: C19H20BrClN2O3S
  • MW: 471.8
  • Catalog: γ-secretase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

NALTRIBEN MESYLATE

Naltriben is a selective δ2-opioid receptor antagonist and TRPM7 activator. Naltriben enhances glioblastoma cell migration and invasion. Naltriben can be used in research into neurological diseases and cancer[1][2].

  • CAS Number: 111555-58-9
  • MF: C26H25NO4
  • MW: 415.48
  • Catalog: Opioid Receptor
  • Density: 1.5 g/cm3
  • Boiling Point: 605.3ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 319.9ºC

Tazomeline

Tazomeline is a selective M1 muscarinic receptor agonist. Tazomeline inhibits twitch height in rabbit vas deferens(IC50= 0.001 nM). Tazomeline can be used for research of neuropsychiatric disorders[1].

  • CAS Number: 131987-54-7
  • MF: C14H23N3S2
  • MW: 297.48300
  • Catalog: mAChR
  • Density: 1.15g/cm3
  • Boiling Point: 407.8ºC at 760mmHg
  • Melting Point: N/A
  • Flash Point: 200.4ºC

Ecopipam hydrochloride

Ecopipam (SCH 39166) hydrochloride is a potent, selective and orally active antagonist of dopamine D1/D5 receptor, with Kis of 1.2 nM and 2.0 nM, respectively. Ecopipam hydrochloride shows more than 40-flod selectivity over D2, D4, 5-HT, and α2a receptor (Ki=0.98, 5.52, 0.08, and 0.73 μM, respectively). Ecopipam hydrochloride can be used for the research of schizophrenia, cocaine addition, and obesity[1][3].

  • CAS Number: 190133-94-9
  • MF: C19H21Cl2NO
  • MW: 350.28200
  • Catalog: 5-HT Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Epi-galanthamine-O-methyl-d3

Epi-galanthamine-O-methyl-d3 is the deuterium labeled Epi-galantamine. Epi-galantamine is a diastereomer of Galantamine. Epi-galantamine is an alkaloid isolated from the bulbs and flowers of Caucasian snowdrop (Galanthus woronowii). Epi-galantamine inhibits AChE with an EC50 of 45.7 μM[1][2][3].

  • CAS Number: 1217655-71-4
  • MF: C17H18D3NO3
  • MW: 290.37
  • Catalog: AChE
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Melatonin receptor agonist 1

Melatonin receptor agonist 1 (compound 20c) is a potent melatonin receptor (MT) agonist, with Ki values of 108 nM (MT2) and 1140 nM (MT1)[1].

  • CAS Number: 2411150-76-8
  • MF: C15H19N3O2
  • MW: 273.33
  • Catalog: Melatonin Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Monepantel

Monepantel is organic anthelmintic, and acts as a positive allosteric modulator of a nematode-specific clade of nicotinic acetylcholine receptor (nAChR) subunits.

  • CAS Number: 887148-69-8
  • MF: C20H13F6N3O2S
  • MW: 473.39200
  • Catalog: nAChR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Aβ-IN-5

Aβ-IN-5 (Compound e12) is an orally active Aβ aggregation inhibitor. Aβ-IN-5 also inhibits AChE and BuChE with IC50 values of 21.29 μM and 1.32 μM, respectively. Aβ-IN-5 shows excellent neuroprotective effects and low neurotoxicity[1].

  • CAS Number: 2417977-65-0
  • MF: C21H20N2O3
  • MW: 348.40
  • Catalog: AChE
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

SB 271046 (Hydrochloride)

SB271046 Hcl is a potent, selective and orally active 5-HT6 receptor antagonist with pKi of 8.9.IC50 Value: 8.9(pKi)Target: 5-HT6 Receptorin vitro: SB 271046 hydrochloride is a sulfonamidal benzothiophene derivative that has been shown to act as a selective 5-HT6 antagonist with pKi values of 9.02-8.92, 6.55, 6.35, 6.27, 6.05, 5.95, 5.76, 5.73, 5.62, 5.55, 5.41, 5.39, 5.27 and < 4.99 for 5-HT6, 5-HT1D, 5-HT1A, D3, 5-HT1B, 5-HT1F, α1B, 5-HT2C, 5-HT2A, D2, 5-HT2B, 5-HT7, 5-HT4 and 5-HT1E respectively, and is > 200-fold selective over 55 other receptors, enzymes and ion channels.in vivo: SB-271046 is moderately brain penetrant (10%), subject to low blood clearance (7.7 mL/min/kg) with a good half-life in rats (4.8 hours), and has excellent oral bioavailability (>80%). SB-271046 produces 3-fold and 2-fold increases in extracellular glutamate levels in both frontal cortex and dorsal hippocampus of rats, respectively, which may be used for the treatment of cognitive and memory dysfunction. SB-271046 (20 mg/kg, orally gavage) 30 min prior to training Wistar rats, is found to reverse significantly the amnesia produced by administering scopolamine (0.8 mg/kg, i.p.) in the 6 hours post-training period. SB-271046 progressively and significantly decreases platform swim angle and escape latencies over the five sequential trials on four consecutive daily sessions compared to vehicle-treated controls in aged rats. SB-271046 also improves task recall as measured by significant increases in the searching of the target quadrant on post-training days 1 and 3. SB-271046 (10 mg/kg, s.c.) produces a significant, tetrodotoxin-dependent, increase in extracellular levels of both glutamate and aspartate within the frontal cortex of rats, reaching maximum values of 375.4% and 215.3% of preinjection values, respectively.

  • CAS Number: 209481-24-3
  • MF: C20H23Cl2N3O3S2
  • MW: 488.45
  • Catalog: 5-HT Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Cyclobuxine D

Cyclobuxine D is a steroidal alkaloid extracted from Buxus microphylla. Cyclobuxine D has a significant bradycardic effect in the rat heart and an inhibitory action on acetylcholine and Ba++−induced contraction of the longitudinal muscle isolated from the rabbit jejunum[1][2].

  • CAS Number: 2241-90-9
  • MF: C25H42N2O
  • MW: 386.61400
  • Catalog: mAChR
  • Density: 1.08g/cm3
  • Boiling Point: 494.2ºC at 760mmHg
  • Melting Point: 236-238ºC
  • Flash Point: 53.5ºC

CGP 55845 hydrochloride

CGP55845 hydrochloride is a potent and selective GABAB receptor antagonist with an IC50 of 6 nM. CGP55845 hydrochloride can be used for neurological research[1][2].

  • CAS Number: 149184-22-5
  • MF: C18H22Cl2NO3P
  • MW: 402.25200
  • Catalog: GABA Receptor
  • Density: 1.332g/cm3
  • Boiling Point: 647.9ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 345.6ºC

Imipramine-d6

Imipramine-d6 is the deuterium labeled Imipramine hydrochloride. Imipramine hydrochloride inhibits serotonin transporter with an IC50 value of 32 nM. Imipramine hydrochloride is reported to prevent the translocation of aSMase, inhibiting MV and exosomes secretion[1][2][3][4][5].

  • CAS Number: 65100-45-0
  • MF: C19H18D6N2
  • MW: 286.44400
  • Catalog: Serotonin Transporter
  • Density: 1.064g/cm3
  • Boiling Point: 403.089ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 179.73ºC

Ambutonium bromide

Ambutonium bromide is an acetylcholine antagonist.

  • CAS Number: 115-51-5
  • MF: C20H27BrN2O
  • MW: 391.34500
  • Catalog: mAChR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Clorpyrifos

Chlorpyrifos is an organophosphate insecticide that is classified as a phosphorothionate. The oxon metabolite of Chlorpyrifos is an inhibitor of acetylcholinesterase (AChE), affecting neurological function in insects, humans, and other animals. The Chlorpyrifos oxon (CPO) metabolite is hydrolyzed by the plasma enzyme paraoxonase 1 (PON1), and susceptibility to neurotoxicity associated with CPO exposure is mitigated by PON1 overexpression.

  • CAS Number: 2921-88-2
  • MF: C9H11Cl3NO3PS
  • MW: 350.586
  • Catalog: AChE
  • Density: 1.5±0.1 g/cm3
  • Boiling Point: 375.9±52.0 °C at 760 mmHg
  • Melting Point: 42-44°C
  • Flash Point: 181.1±30.7 °C

(S)-Amisulpride

(S)-Amisulpride (Esamisulpride) is a potent dopamine D2/D3 receptor antagonist. (S)-Amisulpride is an antagonist at the 5-HT7 receptor with a KI of 900 nM. (S)-Amisulpride has antipsychotic and antidepressant effects[1][2].

  • CAS Number: 71675-92-8
  • MF: C17H27N3O4S
  • MW: 369.48
  • Catalog: 5-HT Receptor
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 558.9±50.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 291.8±30.1 °C

2-piperidin-1-ylethyl 4-amino-5-chloro-2-methoxybenzoate

ML 10302 is a potent agonist 5-HT4 receptor with Ki of 1.07 nM. 5-Hydroxytryptamine (5-HT4) receptor agonists stimulate gut motility through cholinergic pathways. ML10302 induces significant prokinesia both in the small bowel and colon through activation of cholinergic pathways. ML 10302 also has the potential for the research of neurology diseases[1].

  • CAS Number: 148868-55-7
  • MF: C15H21ClN2O3
  • MW: 312.79200
  • Catalog: 5-HT Receptor
  • Density: 1.223g/cm3
  • Boiling Point: 472.7ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 239.7ºC

MK-212

MK-212 (CPP) monohydrochloride is a centrally acting 5-HT1C/5-HT2 agonist. MK-212 monohydrochloride can stimulate phosphoinositide hydrolysis in cerebral cortex[1].

  • CAS Number: 61655-58-1
  • MF: C8H12Cl2N4
  • MW: 235.11400
  • Catalog: 5-HT Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Loxapine

Loxapine Succinate is a D2DR and D4DR inhibitor, serotonergic receptor antagonist and also a dibenzoxazepine anti-psychotic agent.IC50 value: Target: D2DR/D4DR; 5-HT receptorin vitro: In the presence of Loxapine, [3H]ketanserin binds to 5-HT2 receptor in Frontal cortex of brain in human and bovine with ki value of 6.2 nM and 6.6 nM, respectively. Loxapine has the rank order of potency for the various receptors appears to be as follows:5-HT2≥D4>>>D1>D2 in comparing competition experiments involving the human membranes [1]. Loxapine 0.2 μM, 2 μM and 20 μM reduces IL-1beta secretion by LPS-activated mixed glia cultures after 1 and 3 days of exposure. Loxapine in concentrations of 0.2 μM, 2 μM and 20 μM reduces IL-2 secretion in mixed glia cultures after 1 and 3 days of exposure, and additionally Loxapine decreases IL-1beta and IL-2 secretion in LPS-induced microglia cultures in concentrations of 2 μM, 10 μM and 20 μM [2].in vivo: Loxapine (5 mg/kg) induces a very significant reduction (more than 50%) of serotonin (S2) receptor density after 4 weeks or 10 weeks of daily injection in the rat. Loxapine (5 mg/kg) does not change dopamine receptor density but greatly reduces serotonin receptor density by 47% in the brain of rats [3].

  • CAS Number: 1977-10-2
  • MF: C18H18ClN3O
  • MW: 327.80800
  • Catalog: 5-HT Receptor
  • Density: 1.2299 (rough estimate)
  • Boiling Point: N/A
  • Melting Point: 109-110°
  • Flash Point: N/A

(±)-Duloxetine hydrochloride

(±)-Duloxetine ((Rac)-Duloxetine) hydrochloride is the racemate of Duloxetine hydrochloride. Duloxetine hydrochloride, a serotonin-norepinephrine reuptake inhibitor, can be used for diabetic neuropathic pain and fibromyalgia as well as major depressive disorder research[1].

  • CAS Number: 947316-47-4
  • MF: C18H20ClNOS
  • MW: 333.87600
  • Catalog: Serotonin Transporter
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

GSK-1521498

GSK1521498 free base is a potent and selective μ-opioid receptor (MOR) antagonist. GSK1521498 free base is being used for the treatment of disorders of compulsive consumption of food, alcohol, and drugs[1].

  • CAS Number: 1007573-18-3
  • MF: C24H20F2N4
  • MW: 326.34300
  • Catalog: Opioid Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Apimostinel

Apimostinel is an oral NMDA receptor partial agonist.

  • CAS Number: 1421866-48-9
  • MF: C25H37N5O6
  • MW: 503.591
  • Catalog: iGluR
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 878.7±65.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 485.2±34.3 °C

H-Glu(OtBu)-OtBu.HCl

H-Glu(OtBu)-OtBu hydrochloride is a glutamate derivative that can be used for substance P antagonist synthesis[1].

  • CAS Number: 32677-01-3
  • MF: C13H26ClNO4
  • MW: 295.803
  • Catalog: Neurokinin Receptor
  • Density: 1.02g/cm3
  • Boiling Point: 311.1ºC at 760 mmHg
  • Melting Point: 60 to 75ºC
  • Flash Point: 78.1ºC

Tanshinone IIA anhydride

Tanshinone IIA anhydride is a potent and irreversible human carboxylesterase (CE) inhibitor with Ki values of 1.9 nM and 1.4 nM for human CE1 and the human intestinal CE (hiCE), respectively[1].

  • CAS Number: 61077-78-9
  • MF: C19H18O4
  • MW: 310.34
  • Catalog: AChE
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A